A case report and description of the pharmacokinetic behavior of intrapleurally instilled etoposide

Abstract

Etoposide, at a dosage of 100 mg/m2 (156 mg in 250 ml 0.154 M NaCl), was instilled through a thoracostomy tube into the left pleural cavity of a 60-year-old woman with diffuse histiocytic lymphoma and a refractory, recurrent, malignant left pleural effusion. Etoposide concentrations in plasma and pleural cavity fluid were measured by a reverse-phase HPLC system with a C18-reverse phase column, a mobile phase of methanol: H2O (55:45) pumped at 1.2 ml/min, and detection by absorbance at 254 nm. Pleurodesis was successfully accomplished by this maneuver and there were no adverse clinical consequences. Absorption of etoposide from the pleural cavity was slow (approximately 0.2 ml/min). The pleural cavity exposure to etoposide, as measured by the area under the curve, was 46 times greater than if a similar dose had been given IV. Conversely, systemic exposure to etoposide, as assessed by plasma AUC, was less than 50% that associated with IV injection of a similar dose.